ZIC4

Protein identityUniProt · HPA

UniProt accession

Q8N9L1

Gene

ZIC4

Ensembl

ENSG00000174963

Chromosome

3

Canonical length

334 aa

Protein class

Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development, and have been associated with X-linked visceral heterotaxy and holoprosencephaly type 5. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 1, a related family member on chromosome 3. Heterozygous deletion of these linked genes is involved in Dandy-Walker malformation, which is a congenital cerebellar malformation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Dec 2009]

Canonical amino-acid sequenceUniProt

334 residues, UniProt reviewed canonical sequence.

>Q8N9L1|ZIC4
     1  MRYKTSLVMR KRLRLYRNTL KESSSSSGHH GPQLTAASSP SVFPGLHEEP PQASPSRPLN
    61  GLLRLGLPGD MYARPEPFPP GPAARSDALA AAAALHGYGG MNLTVNLAAP HGPGAFFRYM
   121  RQPIKQELIC KWLAADGTAT PSLCSKTFST MHELVTHVTV EHVGGPEQAN HICFWEECPR
   181  QGKPFKAKYK LVNHIRVHTG EKPFPCPFPG CGKVFARSEN LKIHKRTHTG EKPFRCEFEG
   241  CERRFANSSD RKKHSHVHTS DKPYTCKVRG CDKCYTHPSS LRKHMKVHGR SPPPSSGYDS
   301  ATPSALVSPS SDCGHKSQVA SSAAVAARTA DLSE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZIC4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.53

Highest tissue expression

92 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for ZIC4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.87

gnomAD pLI

0

gnomAD missense Z

-0.11

DepMap mean gene effect

0.09

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• central nervous system development
• regulation of transcription by RNA polymerase II

Molecular functions

• DNA binding
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• zinc ion binding

Cellular components

• nucleus

Protein domainsUniProt · Pfam · InterPro

• Zinc finger C2H2-type
• Zinc finger C2H2 superfamily
• ZIC protein, zinc finger domain
• C2H2-type zinc-finger protein GLI-like
• ZIC1-5/GLI1-3like, C2H2 zinc finger
• Zinc finger, C2H2 type
• Zic proteins zinc finger domain
• C2H2 zinc finger

KeywordsUniProt

• DNA-binding
• Metal-binding
• Nucleus
• Repeat
• Zinc
• Zinc-finger